An increasing number of experiments and clinical trials have demonstrated the safety, feasibility, and efficacy of mesenchymal stem cells (MSCs)‐based therapies for the treatment of various diseases. ...The main drawbacks of MSC therapy are the lack of specific homing after systemic infusion and early death of injected cells because of the injury micro‐environment. We pretreated bone mesenchymal stem cells (BMSCs) with erythropoietin (EPO) to investigate their positive effect on cyclosporine A (CsA)‐induced nephrotoxicity. BMSCs were incubated with different concentrations of EPO (10, 100, 500, and 1000 IU/mL) for 24 and 48 h, and their proliferation rate, cytoskeletal morphology, migration ability, and the expression of CXCR4 were evaluated to determine the optimal pretreatment conditions. To investigate the therapeutic effects of BMSCs pretreated with EPO in CsA‐induced nephrotoxicity, we established CsA‐induced in vitro and in vivo toxicity models. In our in vitro study, preconditioning of BMSCs with 500 IU/mL EPO for 48 h induced a marked increase in their proliferation rate, cytoskeletal rearrangement, migration in the scrape‐healing assay, and migration toward injured HK2 cells. In vivo, EPO‐BMSCs showed higher ability to improve renal function than BMSCs, and in CsA‐induced rats treated with EPO‐BMSCs, interstitial lymphocyte infiltration, tubular swelling, necrosis, and interstitial fibrosis decreased. We demonstrated that pretreatment with 500 IU/mL EPO before infusion markedly increased the homing ability of BMSCs, and obviously ameliorate CsA‐induced nephrotoxicity in rats.
We demonstrated that pretreatment with 500 IU/mL EPO before infusion markedly increased the homing ability of BMSCs, and obviously ameliorate CsA‐induced nephrotoxicity in rats.
To explore the enhancement features of early hepatocellular carcinoma (HCC, including well-differentiated HCC and high-grade dysplastic nodules with a focus of HCC) and high-grade dysplastic nodules ...(HGDNs) on contrast-enhanced ultrasound (CEUS), correlated with the histopathologic findings.
This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings.
Thirty-eight (55.1%) early HCCs showed arterial-phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late-phase wash-out (20 of 69 29.0%). Eight (11.6%) early HCCs manifested APHE. Wash-out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very-late wash-out (>120 seconds). Wash-out was not observed in all HGDNs. Of the 16 HGDNs, arterial-phase isoenhancement without portal venous/late-phase wash-out was the major enhancement pattern (n = 7 43.8%). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P = .001). Arterial-phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P = .039).
Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.
Abstract
Background
Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after ...systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect, however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment.
Results
We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated silent information regulator 1 (SIRT1) and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did.
Conclusions
Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.
Objectives. To investigate the value of contrast-enhanced ultrasound (CEUS) in guidance of percutaneous biopsy in peripheral pulmonary lesions. Methods. This study focused on 53 patients (male: 38, ...female: 15, and mean age: 55.7 years ± 10.7) with 53 single peripheral pulmonary lesions. Before core needle (16-gauge) percutaneous biopsy, CEUS were performed in all lesions, with injection of 2.4 mL SonoVue (Bracco, Italy). The contrast-enhancement pattern, display rate of internal necrosis (nonenhanced) and active (obviously enhanced) areas, biopsy success rate, and pathological diagnosis rate were recorded. Results. All the peripheral pulmonary lesions were proved pathologically as benign lesions (n=7), primary malignancies (n=41), or metastasis (n=5). Forty (86.9%) malignant lesions and 4 (57.1%) benign lesions showed internal necrosis areas on CEUS. The detection rate and average size of internal necrosis areas had been significantly improved compared to conventional ultrasound (P<0.05). After CEUS, core needle percutaneous biopsies were performed successfully in the active areas of all lesions. The sampling success rate and pathological diagnosis rate were 100% and 98.1%. Conclusions. CEUS before biopsy provided useful diagnostic information about peripheral pulmonary lesions. By depicting internal necrotic and active areas, it is a promising technique for guaranteeing the accuracy, success, and safety of core needle biopsy.
This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.
This retrospective ...study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.
No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.
CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.
We aimed to explore the value of contrast-enhanced ultrasonography (CEUS) in guidance of percutaneous biopsy of anterior mediastinal lesions.
Ninety patients with solitary anterior mediastinal ...lesions (55 males, 35 females; mean age, 46±4 years) were included. Patients were randomly divided into CEUS group (n=45) and conventional ultrasonography (US) group (n=45). Real-time US-guided core needle (16 G) percutaneous biopsies were performed in all lesions. The display of internal mammary arteries, internal necrosis, and active areas were recorded and compared. Biopsy success rate and diagnostic accuracy were compared between the two groups.
Display rate of unenhanced internal necrosis was higher in the CEUS group than in the US group (88.9% vs. 46.7%, P = 0.041). With real-time CEUS guidance, internal mammary arteries were effectively displayed and avoided during biopsies in 68.9% of the lesions (31/45). Of the lesions, 88.9% (80/90) were histologically proven, including 13 benign lesions and 67 malignancies. There was a significant difference in the rate of successful puncture attempts between the two groups (P = 0.041). CEUS group had a higher biopsy success rate (100% vs. 95.5%, P = 0.045) and higher diagnostic accuracy (97.8% vs. 82.2%, P = 0.035) compared with the US group (P = 0.035).
CEUS guidance is a promising technique in depicting internal necrotic areas, viable areas, and internal mammary arteries during percutaneous biopsy of anterior mediastinal lesion, with satisfying safety, accuracy, and success rates.
Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the ...neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia.
The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods.
The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups.
Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.
The purpose of this study is to evaluate quantitative analysis of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of renal tumor histotypes.
Between January 2010 and December 2013, ...106 clear cell renal cell carcinomas (RCCs) (mean ± SD diameter, 3.7 ± 1.8 cm), 34 angiomyolipomas (mean diameter, 4.1 ± 1.4 cm), 25 papillary RCCs (mean diameter, 3.5 ± 1.1 cm), and 28 chromophobe RCCs (mean diameter, 2.9 ± 0.9 cm) underwent CEUS quantitative analysis. The dynamic vascular pattern was analyzed with the Fisher exact chi-square test, and rise time, time to peak (TTP), and tumor-to-cortex enhancement ratio were analyzed with the independent-sample t test.
Dynamic vascular pattern types I and III (hyperenhancement) were more common among clear cell RCCs, whereas type II (hypoenhancement) was more common among angiomyolipomas, papillary RCCs, and chromophobe RCCs. Irrespective of dynamic vascular pattern class, the rise time and TTP were the shortest in clear cell RCCs and were equal in angiomyolipomas, papillary, and chromophobe RCCs. The tumor-to-cortex enhancement ratio was the highest in clear cell RCCs, was second highest in angiomyolipomas, and was lowest but equal in papillary and chromophobe RCCs. Clear cell RCCs and angiomyolipomas accounted for the majority of the hyperenhancing group. The tumor-to-cortex enhancement ratio of clear cell RCCs was higher than that of angiomyolipomas. With tumor-to-cortex enhancement ratio greater than 146.0% as the cutoff to differentiate clear cell RCC from angiomyolipoma in the hyperenhanced group, the sensitivity and specificity were each 71.4%. In the hypoenhanced group, the tumor-to-cortex enhancement ratio was the same in clear cell RCCs and angiomyolipomas but was higher in papillary and chromophobe RCCs. With tumor-to-cortex enhancement ratio greater than 54.2% as the cutoff point to differentiate clear cell RCCs from papillary and chromophobe RCCs, the sensitivity and specificity were 95.5% and 94.8%, respectively, whereas with a tumor-to-cortex enhancement ratio greater than 57.4% as the cutoff point to differentiate angiomyolipomas from papillary and chromophobe RCCs, the sensitivity and specificity were 90.0% and 96.4%, respectively.
Quantitative analysis of CEUS can show quantification of enhancement features of different renal tumor histotypes and may be helpful in their differential diagnosis.
Recurrence or metastasis after surgery had been reported in hepatic epithelioid angiomylipoma (epi-AML). Most hepatic epi-AMLs were misdiagnosed with hepatocellular carcinoma or other hepatic tumors ...before surgery.
To describe the baseline and contrast-enhanced ultrasound (CEUS) features of hepatic epi-AMLs and to explore the potential ultrasonic features for prognosis.
The retrospective study enrolled 67 patients (56 females, 11 males) with 67 pathologically confirmed hepatic epi-AML lesions. All the lesions were examined by baseline ultrasound and 42 lesions were examined using CEUS with SonoVue (Bracco, Milan, Italy) before surgery.
Baseline ultrasound features of hepatic epi-AMLs included heterogeneous echo (86.6%), well-defined border (68.7%), hypoecho (64.2%), regular morphology (62.7%), peripheral-tumor arc-shaped or ring-like vessels (53.7%), and low value of resistive index (0.51±0.08). CEUS features of hepatic epi-AMLs included arterial phase hyper-enhancement with smooth and well-defined margin (100%), peripheral-tumor ring-like vessels (57.1%), and intra-tumor vessels (52.4%). Some CEUS features, including arterial phase heterogeneously tortuous filling, intra-tumor vessels and peripheral-tumor ring-like vessels were more commonly found in hepatic epi-AMLs of uncertain malignant potential/malignant than in benign hepatic epi-AMLs (p < 0.05).
Baseline ultrasound and CEUS features may be useful in diagnosis of hepatic epi-AML, and some CEUS features may be indicative of its malignant potential.
Objectives
To identify features which determine the papillary nature of breast lesions by contrast-enhanced ultrasound (CEUS) based on morphological and pathological correlations, and predict which ...papillomas are malignant.
Methods
A retrospective review of 47 papillary lesions and 51 hypervascular benign abnormalities was performed. Enhancement patterns and diagnostic performance of CEUS were assessed.
Results
The most frequent finding in papillary lesions was perilesional linear ductal enhancement (87.2 %) followed by heterogeneous enhancement (80.9 %), and the presence of perfusion defects (66 %). Among all CEUS morphological descriptors, a perilesional linear ductal enhancement pattern was the most effective feature to discriminate between papillary and hypervascular benign lesions. Using this criterion, the positive and negative predictive value for papilloma were 100 % and 89.5 %, respectively. A perilesional linear ductal pattern correlated with a ductal origin. The distinctive features associated with atypical or malignant papillomas were non-confluent enhancement, late overall wash-out, the presence of regional perfusion defect, clumped vascular pattern, and the presence of peripheral radial or penetrating vessels. The sensitivity, specificity, and positive and negative predictive values for predicting malignancy were 91.7 %, 82.6 %, 84.6 % and 90.5 %, respectively.
Conclusions
CEUS provided characteristic enhancement patterns which could be helpful for identifying papillary lesions and for predicting potentially malignant papillomas.
Key Points
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Papillary breast lesions display a characteristic appearance on CEUS
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Adding CEUS to conventional US helps identify the papillary nature of papillomas
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CEUS may be helpful for predicting potential malignancies among papillomas
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